Mass spectrometry (MS) is an analytical technique for determining the elemental composition of a sample or molecule, or for elucidating the chemical structures of molecules, such as peptides and other chemical compounds. Mass spectrometry generally includes ionizing chemical compounds to generate charged molecules or molecule fragments and then measuring of their mass-to-charge ratios. In a typical MS procedure, a sample loaded onto a mass spectrometer undergoes vaporization and the components of the sample are ionized to form charged particles (ions). The ions are typically accelerated by an electric field for computation of the mass-to-charge ratio (m/z) of the particles based on the details of motion of the ions as they move through electromagnetic fields. The ions may be sorted by a mass analyzer according to their mass-to-charge ratio (m/z) and detected by a detector for measuring the value of an indicator quantity and providing data for calculating the abundances of each ion present. The calculated mass of each ion may change or drift during operation of the mass spectrometer, due to various factors.
One approach (“Lock Mass”) that is used to address the variable mass involves adding one or more known chemicals with known masses into the sample that is being analyzed. This introduction of chemicals will then generate spectral peaks with known masses allowing each mass spectrum to be individually mass calibrated using these spectral peaks. But because the added chemicals are supplied in low quantities to prevent them from interfering with the sample under analysis, poor mass precision for the spectral peaks may result leading to a lower quality mass calibration due to statistical variation. The use of a small number of lock mass can transfer mass variation from the lock mass to all other masses. In the single lock mass case, the lock mass exhibits no mass variation. This makes all other masses within the spectrum more variable.
Also, background calibrant that is used in some known techniques is usually a dilute background so that ionization capacity is not significantly reduced. This low concentration may make for statistically poor drift estimates on individual spectrum.
This method also involves finding the lock mass within the spectrum and because small quantities of the lock mass calibrants are introduced, they can be difficult to identify, especially in rich spectra as other interfering spectral peaks may be near the lock mass peak. This introduces the potential for significant error if the wrong spectral peak is selected as the lock mass peak. Further, this approach requires that the user specify the exact masses of the calibrants and ignores the potentially higher intensity background ions that are often persistent in varying degrees throughout the analysis.